Background: Pulmonary embolism is the leading cause of death in pregnancy and the puerperium – accounting for nearly 20% of maternal deaths in the United States – making rapid and accurate diagnosis critically important for emergency physicians, OB/GYNs, and all who take care of these women on a regular basis. Unfortunately, typical diagnostic pathways and approaches may not apply in pregnancy, and are made more complicated by the frequency of concerning and suggestive signs and symptoms in this population, particularly dyspnea (a common symptom in pregnancy related to an increase in progesterone levels) and tachycardia (as resting heart rate is typically expected to increase by up to 25% in normal pregnancy).

While the use of the D-dimer in conjunction with a low pre-test probability for pulmonary embolism is well established for ruling out PE in the non-pregnant population, the preponderance of evidence to date suggests significant shortcomings with such a strategy in pregnant patients. Indeed, the American Thoracic Society guidelines [1] recommend specifically against the use of D-dimer to exclude PE in pregnancy. Still, though, many emergency physicians have striven for a rational approach to diagnosis—limiting radiation exposure while ensuring safety and sensitivity. The “Kline Algorithm,” as best described in this 2013 podcast on Rob Orman’s venerable ERCast, draws on physiologic expectations and the expertise of Jeff Kline, MD, an emergency medicine physician and expert in venous thromboembolism, to propose a more sensible approach to diagnosis. Unfortunately, literature to support this approach has been sparse. The DiPEP study, published recently in the British Journal of Haematology, attempted to add to this literature base [2].

Sensitivity of D-dimer assay excluding patients who had received anticoagulant (Secondary Outcome)

66 total patients included, only 4 of whom had VTE

ELISA assay ≈ 50%

INNOVANCE POC assay ≈ 25%

No significant difference noted among any of an expanded list of biomarkers.

BNP, Troponin, CRP, PT, APTT, etc.

Strengths:

Largest study to date examining the utility of biomarkers for PE in pregnancy and puerperium.

Though the predicted PE prevalence rate (2%) was very low, augmentation of patients with diagnosed DVT permitted mirroring of the expected rate of VTE in the study population.

Diagnosis of PE made by independent assessors blinded to D-dimer results.

D-dimer measured using both ELISA and POC testing to account for real-world variation in testing modalities.

Limitations:

No information provided as to duration of postpartum period included in study.

Observational nature prevents utilization of D-dimer based on pre-test probability of disease/risk stratification.

Cardiac strain (and thus many of the other biomarkers investigated in this study) is likely to be much lower in DVT than PE, making cardiac biomarkers less sensitive in DVT than PE. Study augmentation of patients diagnosed with DVT may have clouded these results.

The overwhelming majority of patients received anticoagulation prior to blood sampling, severely limiting the applicable patient population for analysis.

Discussion:

Given the significant limitations of this study, it adds very little to the knowledge base surrounding the use of D-dimer for the evaluation of pulmonary embolism in pregnancy.

The study highlights the paucity of relevant literature, however, and reminds physicians of guidelines recommending against the use of D-dimer.